Outlook Therapeutics FDA Rejection

robertbanking

Hello you wonderful and intelligent people that make up this forum. I sincerely hope things are going well for you.

I was recently looking through Biotechnology company's stocks/investments and found a company named Outlook Therapeutics. There drug for wet AMD (this is when abnormal blood vessels grow in the back of the eye and damage the macula) did not get approved due to manufacturing issues observed during pre-approval inspections. I kindly wondered please if anyone knows what this means and shouldn't the company have declared these manufacturing issues, which they would have known about before the FDA rejection please? If anyone kindly had any thoughts on this i would be forever grateful and thankful it would mean the world to me.

Sending you lots of good wishes and i truly hope everything continues to go well for you. All the very best and look after yourself. Hope you stay happy and healthy.  

masonic

So this is ONS-5010, which is reformulated version of the Genentech monoclonal antibody Avastin, for injection into the eye rather than IV. It looks like the FDA was unsatisfied when they inspected the manufacturing process back in August, so it appears the company unaware of the issues, either because it was ignorant of the standards required or didn't carry out its own due diligence of the manufacturing facilities. "Lack of substantial evidence" was also mentioned as a reason for the rejection. The former may be resolvable, whereas the latter might not - they'll need to run another clinical study to address this which will delay them by about a year. It appears they are now panicking and taking a scattergun approach to their regulatory applications, which is understandable in the circumstances.

The main question you should ask yourself is, given that IV Avastin is currently being repurposed and used off label in the absence of a specific formulation for this indication, what will happen when it goes off-patent - the first patent expires later in 2024? Seems like a generic intravitreal product could be just around the corner. What IP will prevent this?

aroominyork

Thank you, masonic, for clarifying that biotech investing is really quite straigtforward. It's just about getting your ideas approved and selling your kit with a decent margin. Probably easier than understanding McDonald's business model with all those seasonal variations and different menus; after all, people will always have eye problems that need treating.

robertbanking

Thank you very much masonic for your very helpful response, that is very kind of you. I really appreciate the time you took to reply, you are a very wonderful person.

I have been interested in a few biotechnology stocks, however i have tried to learn from not only company's that did well, but company's that have not done so well. It appears the largest issue for the company is the lack of substantial evidence, in which they will need to run further clinical trials, which is not good. You also raise a very important point when the product also goes off patent, competing firms could easily bring in substitute or similar products. I really appreciate your help understanding this masonic, you are a very amazing person and a credit to these forums.

Sending you lots of good wishes and i truly hope you continue to have a wonderful life and everything goes well for you masonic. All the very best and take care.  

masonic

aroominyork said:

Thank you, masonic, for clarifying that biotech investing is really quite straigtforward. It's just about getting your ideas approved and selling your kit with a decent margin. Probably easier than understanding McDonald's business model with all those seasonal variations and different menus; after all, people will always have eye problems that need treating.

If only picking the ones that will be successful was as straightforward. My only exposure to the sector is through my employment, and it is necessary to build up quite a resilience to failures.

robertbanking

Can i please ask you Masonic, if you know how the public can obtain information on a company's manufacturing process please? I would have thought given the FDA but so much emphasis on this, it would need to be disclosed in public documents to investors but it is not. If you kindly please had any thoughts on this i would be forever grateful and thankful it would mean the world to me. Hope you have a fantastic week Masonic and all the very best to you.  

masonic

robertbanking said:

Can i please ask you Masonic, if you know how the public can obtain information on a company's manufacturing process please? I would have thought given the FDA but so much emphasis on this, it would need to be disclosed in public documents to investors but it is not. If you kindly please had any thoughts on this i would be forever grateful and thankful it would mean the world to me. Hope you have a fantastic week Masonic and all the very best to you.  

The short answer is that you won't. These details will be a closely guarded secret, as it will be a source of competitive advantage for the company. If there was something patentable within the CMC programme, then you might be able to get some insights when a patent application publishes, but this will be 18+ months after it was first filed, and what would need to be disclosed in such an application would be very limited indeed, so unlikely to be relevant to the FDA's concerns. If I were to take a wild guess, it would be that Outlook, being a biotech with little infrastructure of its own, engaged a CMC consultancy and placed the manufacturing programme with a CDMO. One or both of these parties didn't do a good enough job on the regulatory compliance front. It's pure speculation as to what was lacking, but to illustrate with an example, a manufacturing process should be able to perform with consistency, limit the formation of impurities and degradants, and have these qualified and being monitored throughout the campaign. There are obviously many other such requirements, any of which could give rise to concern if not adequately addressed.

robertbanking

Thank you very much for your very helpful response Masonic, you are a star, i really appreciate the very helpful response you kindly provided. I appreciate the details that a manufacturing process should be able to perform with consistency, limit the formation of impurities and degradants, and have these qualified and being monitored throughout the campaign.  

I kindly wondered as a private investor, how you could hopefully increase your chances of success that a biotechnology company would get the manufacturing process correct please? For instance would having a Chief Operating Officer that has experience in CMC management be helpful please? Lastly could you check reviews and details of the outsourced company they used for the manufacturing program please? If you kindly had any thoughts on this it would mean the world to me and i would be forever grateful. Thanks very much for being a wonderful and helpful person Masonic. Very best wishes to you.  

shortseller09

It would mean the world to me and I would be forever grateful if you could just speak normally.

aroominyork

I especially like "check reviews... of the outsourced company". I guess it could be useful: "The crème brûlée in the staff canteen was one of the best I have tasted."

masonic

robertbanking said:

I kindly wondered as a private investor, how you could hopefully increase your chances of success that a biotechnology company would get the manufacturing process correct please? For instance would having a Chief Operating Officer that has experience in CMC management be helpful please? Lastly could you check reviews and details of the outsourced company they used for the manufacturing program please? If you kindly had any thoughts on this it would mean the world to me and i would be forever grateful. Thanks very much for being a wonderful and helpful person Masonic. Very best wishes to you.  

Major investors in a biotech will generally be able to meet with the principals and discuss in detail any aspect of the project. They often engage relevant subject matter experts to do due diligence, wherein they are granted access to a data room containing the relevant information. A private investor doesn't have those sort of resources at their disposal, so have to manage with the very heavily redacted public disclosures made by the company. Looking at the management team and their track record might give you some insight, but every project is different and you can't really know as an outside observer exactly what is going on at a nuts and bolts level, or whether the team are capable of overcoming whatever issues they face. Even with the full information, investors back the wrong horse often enough. It is a high risk sector with many things that can go wrong at each stage of bringing a drug to market.